Eicosanoid, synthesis

A Variety of Stimuli Trigger Arachidonate Release and Eicosanoid Synthesis... 

Besides watet, the diet must provide metaboEc fuels (carbohydrate and fat) fot bodily growth and activity protein fot synthesis of tissue proteins fiber for roughage minerals for specific metabolic functions cettain polyunsamtated fatty acids of the n-3 and n-6 famihes fot eicosanoid synthesis and other functions and vitamins, otganic compounds needed in small amounts for many varied essential functions. 

FIGURE 57-2. Eicosanoid synthesis pathway. Cyclooxygenase is inhibited by nonsteroidal anti-inflammatory drugs and aspirin. (From Widmaier EP, Raff H, Strang KT, et al, (eds.) Vander, Sherman, Luciano s Human Physiology The Mechanisms of Body Function. 9th ed. New York McGraw-Hill 2004, Figure 5-11.)... 

Nitric oxide and eicosanoid synthesis haem synthesis. The importance of the pentose phosphate pathway reduced glutathione in maintaining red cell integrity. The respiratory burst in phagocytes. Clotting and complement enzyme cascades. Metabolism of lipoproteins. 

Eicosanoid synthesis. Arachidonic acid is converted by cyclooxygenases into prostaglandins, and thromboxanes. Lipoxygenases convert arachidonic acid into HPETEs, which are then converted to lipoxins, leukotrienes, and 12-HETE (hydroxyeicosatetraenoic acid). Epoxygenases convert arachidonic acid into epoxides. 

Sambo 1988). Nonsesquiterpene lactones in feverfew were also found to inhibit eicosanoid synthesis with high potency (Sumner et al. 1992). 

There are a number of signs and symptoms of essential fatty acid deficiency. They include scaly and thickened skin, alopecia, increased capillary fragility so that bruising readily occurs, poor wound healing, increased susceptibility to infection and growth retardation in infants and children. Some of these symptoms can be explained by deficiency of eicosanoid synthesis and/or failure to complete cell cycles in various tissues (Chapter 20). Consequently, it is important to detect a deficiency before symptoms develop. The principle underlying the method to do this is described ... 

Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase [2] and consequently the synthesis of most eicosanoids. This explains their analgesic, antipyretic, and antirheumatic effects. Frequent side effects of NSAIDs also result from inhibition of eicosanoid synthesis. For example, they impair hemostasis because the synthesis of thromboxanes by thrombocytes is inhibited. In the stomach, NSAIDs increase HCl secretion and at the same time inhibit the formation of protective mucus. Long-term NSAID use can therefore damage the gastric mucosa. 

Corticosteroids block all the known pathways of eicosanoid synthesis, perhaps in part by stimulating the synthesis of several inhibitory proteins collectively called annexins or lipocortins. They inhibit phospholipase A2 activity, probably by interfering with... 

Corticosteroids and cromolyn are also useful in asthma. Corticosteroids inhibit eicosanoid synthesis and thus limit the amounts of eicosanoid mediator available for release. Cromolyn appears to inhibit the release of eicosanoids and other mediators such as histamine and platelet-activating factor from mast cells. 

Cells of the immune system contribute substantially to eicosanoid biosynthesis during an immune reaction. T and lymphocytes are not primary synthetic sources however, they may supply arachidonic acid to monocyte-macrophages for eicosanoid synthesis. In addition, there is evidence for eicosanoid-mediated cell-cell interaction by platelets, erythrocytes, leukocytes, and endothelial cells. 

The effects of onion and garlic on eicosanoid metabolism have mainly been studied by observing the effects of garlic and onion preparations on platelet aggregation and subsequent eicosanoid synthesis. 

Rose DP, Connolly JM (1990), Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture, Cancer Res. 50 7139-7144. 

Table 4. Fatty acid effects (in vitro) on collagen-induced platelet aggregation and eicosanoid synthesis ...

Data with permission from a thesis on fatty acids and platelet fiinction by Timothy Wilkinson, University Guelph, Guelph, Ontario, Canada (Wilkinson T and Mahadev Murtl M, 1998 unpublished data). Fatty acid effects on platelet aggregation and eicosanoid synthesis, were evaluated in die presence of physiological concentration of albumin. 

Alternatively, the release of platelet phospholipid AA is mediated by the activation of phospholipase Aj (PIA) coupled to PLC, intracellular Ca rise and protein kinase C (PKC) and tyrosine kinase-mediated protein phosphorylations (23,24) and/or by the activation of PLA that is not coupled to these events in platelets (25-29). Furthermore, the hydrolysis of phosphatidic acid (PA) by a PA-specific PLAj may also contribute to eicosanoid synthesis (30,31). It is evident that the differential sensitivity of platelets to multiple agonists and their signals, have contributed to the complexity in understanding the regulation of PLAj. 

Pace-Asciak, C.R., Hahn, S., Diamandis, E.P., Soleas, G. and Goldberg, D.M. (1995) The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis Implications for protection against coronary heart disease, Clin. Chim. Acta, 235(2), 207-219. 

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